Amino Acids, Peptides, and Proteins Commons^™

Atomistic Simulations And In Silico Mutational Profiling Of Protein Stability And Binding In The Sars-Cov-2 Spike Protein Complexes With Nanobodies: Molecular Determinants Of Mutational Escape Mechanisms, Gennady M. Verkhivker, Steve Agajanian, Deniz Yasar Oztas, Grace Gupta

Mathematics, Physics, and Computer Science Faculty Articles and Research

Structure-functional studies have recently revealed a spectrum of diverse high-affinity nanobodies with efficient neutralizing capacity against SARS-CoV-2 virus and resilience against mutational escape. In this study, we combine atomistic simulations with the ensemble-based mutational profiling of binding for the SARS-CoV-2 S-RBD complexes with a wide range of nanobodies to identify dynamic and binding affinity fingerprints and characterize the energetic determinants of nanobody-escaping mutations. Using an in silico mutational profiling approach for probing the protein stability and binding, we examine dynamics and energetics of the SARS-CoV-2 complexes with single nanobodies Nb6 and Nb20, VHH E, a pair combination VHH E + …

Subtype-Selective Positive Modulation Of KCa 2 Channels Depends On The Ha/Hb Helices, Young-Woo Nam, Meng Cui, Naglaa Salem, Razan Orfali, Misa Nguyen, Grace Yang, Mohammad Asikur Rahman, Judy Lee, Miao Zhang

Pharmacy Faculty Articles and Research

Background and Purpose

In the activated state of small-conductance Ca2+-activated potassium (KCa 2) channels, calmodulin interacts with the HA/HB helices and the S4-S5 linker. CyPPA potentiates KCa 2.2a and KCa 2.3 channel activity but not the KCa 2.1 and KCa 3.1 subtypes.

Experimental Approach

Site-directed mutagenesis, patch-clamp recordings and in silico modeling were utilized to explore the structural determinants for the subtype-selective modulation of KCa 2 channels by CyPPA.

Key Results

Mutating residues in the HA (V420) and HB (K467) helices of KCa 2.2a channels to their equivalent residues in KCa 3.1 channels diminished the potency of CyPPA. CyPPA elicited …

Gene Expression Profiling Of Mapk Pathway Inhibitor Resistance In Cutaneous Melanoma: Can Bioinformatics Be Used To Select Better Melanoma Cell Lines?, Stephen Luebker

Theses & Dissertations

Melanoma is the deadliest form of skin cancer, and incidence has continued to increase. Half of all melanomas have a BRAF V600E mutation and respond to MAPK pathway inhibitors, including BRAF inhibitor therapy or BRAF/MEK inhibitor combination therapy, but nearly all patients develop treatment resistance. Melanoma cell lines produce variable results as models of MAPK pathway inhibitor resistance. To better understand how the genomic similarity of a melanoma cell line to patient-derived tumors affects resistance mechanisms, differences in DNA mutations and copy-number alterations were compared between melanoma cell lines profiled by the Cancer Cell Line Encyclopedia and cutaneous melanoma tumors …

Uplc-Ms/Ms Analysis Of The Michaelis-Menten Kinetics Of Cyp3a-Mediated Midazolam 1′- And 4-Hydroxylation In Rat Brain Microsomes, Devaraj Venkatapura Chandrashekar, Barent Dubois, Reza Mehvar

Pharmacy Faculty Articles and Research

Midazolam (MDZ) is a short-acting benzodiazepine with rapid onset of action, which is metabolized by CYP3A isoenzymes to two hydroxylated metabolites, 1′-hydroxymidazolam and 4-hydroxymidazolam. The drug is also commonly used as a marker of CYP3A activity in the liver microsomes. However, the kinetics of CYP3A-mediated hydroxylation of MDZ in the brain, which contains much lower CYP content than the liver, have not been reported. In this study, UPLC-MS/MS and metabolic incubation methods were developed and validated for simultaneous measurement of low concentrations of both hydroxylated metabolites of MDZ in brain microsomes. Different concentrations of MDZ (1–500 µM) were incubated with …

Differential Effect Of Proinflammatory Cytokines On Corneal And Conjunctival Epithelial Cell Mucins And Glycocalyx, Kiumars Shamloo, Priya Mistry, Ashley Barbarino, Christopher Ross, Vishal Jhanji

Pharmacy Faculty Articles and Research

Purpose: Ocular surface mucins and glycocalyx are critical for providing ocular hydration as well lubrication and repelling pathogens or allergens. Elevated levels of tear proinflammatory cytokines in dry eye may have detrimental effect on mucins and glycocalyx. The present study tested the effect of proinflammatory cytokines IL-6, TNF-α, and IFN-γ on membrane-tethered mucins expression, glycocalyx, and viability of ocular surface epithelial cells.

Methods: Stratified cultures of human corneal and conjunctival epithelial cells were exposed to different concentrations of IL-6, TNF-α, and IFN-γ for 24 hours. The mucins gene and protein expressions were quantified by real-time polymerase chain reaction …

Synphilin-1 And Its Effects On Pathogenesis Of Parkinson’S Disease, Mirghani Mohamed

Honors Scholar Theses

Parkinson's Disease (PD) is a progressive neurodegenerative and movement disorder primarily caused by the degradation of dopaminergic neurons. Known markers of neurodegeneration in PD are Lewy Bodies, which are fibrillar aggregates that are found in the brains of PD patients. Lewy Bodies can accumulate from specific mutations in the SNCA gene that codes for alpha-synuclein, a protein enriched in presynaptic neurons. A mutated SNCA gene can cause conformational aggregates of alpha-synuclein to form toxic species mediating neuronal death. Research into alpha-synuclein has led to the discovery of a binding partner known as synphilin-1 that is also found in protein aggregates …

Suppression Of Human Coronavirus 229e Infection In Lung Fibroblast Cells Via Rna Interference, Hamidreza Montazeri Aliabadi, Jennifer Totonchy, Parvin Mahdipoor, Keykavous Parang, Hasan Uludağ

Pharmacy Faculty Articles and Research

Despite extensive efforts to repurpose approved drugs, discover new small molecules, and develop vaccines, COVID-19 pandemic is still claiming victims around the world. The current arsenal of antiviral compounds did not perform well in the past viral infections (e.g., SARS), which casts a shadow of doubt for use against the new SARS-CoV-2. Vaccines should offer the ultimate protection; however, there is limited information about the longevity of the generated immunity and the protection against possible mutations. This study uses Human Coronavirus 229E as a model coronavirus to test the hypothesis that effective delivery of virus-specific siRNAs to infected cells will …

Ciliary Extracellular Vesicles Are Distinct From The Cytosolic Extracellular Vesicles, Ashraf M. Mohieldin, Rajasekharreddy Pala, Richard Beuttler, James J. Moresco, John R. Yates Iii, Surya M. Nauli

Pharmacy Faculty Articles and Research

Extracellular vesicles (EVs) are cell‐derived membrane vesicles that are released into the extracellular space. EVs encapsulate key proteins and mediate intercellular signalling pathways. Recently, primary cilia have been shown to release EVs under fluid‐shear flow, but many proteins encapsulated in these vesicles have never been identified. Primary cilia are ubiquitous mechanosensory organelles that protrude from the apical surface of almost all human cells. Primary cilia also serve as compartments for signalling pathways, and their defects have been associated with a wide range of human genetic diseases called ciliopathies. To better understand the mechanism of ciliopathies, it is imperative to know …

Investigating The Role Of Znf384 Rearrangements In Acute Leukemia, Kirsten Dickerson

Theses and Dissertations (ETD)

Chromosomal rearrangements involving ZNF384 are the defining lesion in 5% of pediatric and adult B-cell acute lymphoblastic leukemia and tumors are characterized by aberrant myeloid marker expression. Additionally, ZNF384 rearrangements are the defining lesion in nearly half of pediatric B/myeloid mixed phenotype acute leukemia. These fusions juxtapose full-length ZNF384 to the N terminal portion of a diverse range of partners, most often, transcription factors or epigenetic modifiers. It has been shown that ZNF384-rearranged tumors have a distinct gene expression profile that is consistent between disease groups and N terminal partners. Genomic analyses of patient tumors has shown that ZNF384 fusions …

The Mechanism Of Β-N-Methylamino-L-Alanine Inhibition Of Trna Aminoacylation And Its Impact On Misincorporation, Nien-Ching Han, Tammy J. Bullwinkle, Kaeli F. Loeb, Kym F. Faull, Kyle Mohler, Jesse Rinehart, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

β-N-methylamino-l-alanine (BMAA) is a nonproteinogenic amino acid that has been associated with neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). BMAA has been found in human protein extracts; however, the mechanism by which it enters the proteome is still unclear. It has been suggested that BMAA is misincorporated at serine codons during protein synthesis, but direct evidence of its cotranslational incorporation is currently lacking. Here, using LC-MS–purified BMAA and several biochemical assays, we sought to determine whether any aminoacyl-tRNA synthetase (aaRS) utilizes BMAA as a substrate for aminoacylation. Despite BMAA's previously predicted misincorporation at serine …

[(Wr)8Wkβa]-Doxorubicin Conjugate: A Delivery System To Overcome Multi-Drug Resistance Against Doxorubicin, Khalid Zoghebi, Hamidreza Montazeri Aliabadi, Rakesh Kumar Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

Doxorubicin (Dox) is an anthracycline chemotherapeutic agent used to treat breast, leukemia, and lymphoma malignancies. However, cardiotoxicity and inherent acquired resistance are major drawbacks, limiting its clinical application. We have previously shown that cyclic peptide [WR]₉ containing alternate tryptophan (W) and arginine (R) residues acts as an efficient molecular transporter. An amphiphilic cyclic peptide containing a lysine (K) residue and alternative W and R was conjugated through a free side chain amino group with Dox via a glutarate linker to afford [(WR)₈WKβA]-Dox conjugate. Antiproliferative assays were performed in different cancer cell lines using the conjugate and the …

Cloning And Functional Characterizations Of Circular Rnas From The Human Mapt Locus, Justin R. Welden

Theses and Dissertations--Molecular and Cellular Biochemistry

Under pathophysiological conditions, the microtubule protein tau (MAPT) forms neurofibrillary tangles that are the hallmark of sporadic Alzheimer’s disease as well as familial frontotemporal dementias linked to chromosome 17 (FTDP-17). In this work, I report that MAPT forms circular RNAs through backsplicing of exon 12 to either exon 10 or exon 7 (12→10; 12→7), and that these circular RNAs are translated into proteins.

Using stable cell lines overexpressing the circular tau RNAs 12→7 and 12→10, we have discovered that the tau circular RNA 12→7 is translated in a rolling circle, giving rise to multiple proteins. This circular RNA …

Bioavailability And Spatial Distribution Of Fatty Acids In The Rat Retina After Dietary Omega-3 Supplementation, Elisa Vidal, Bokkyoo Jun, William C. Gordon, Marie Annick Maire, Lucy Martine, Stéphane Grégoire, Spiro Khoury, Stephanie Cabaret, Olivier Berdeaux, Niyazi Acar, Lionel Bretillon, Nicolas G. Bazan

School of Medicine Faculty Publications

Spatial changes of FAs in the retina in response to different dietary n-3 formulations have never been explored, although a diet rich in EPA and DHA is recommended to protect the retina against the effects of aging. In this study, Wistar rats were fed for 8 weeks with balanced diet including either EPA-containing phospholipids (PLs), EPA-containing TGs, DHA-containing PLs, or DHA-containing TGs. Qualitative changes in FA composition of plasma, erythrocytes, and retina were evaluated by gas chromatography-flame ionization detector. Following the different dietary intakes, changes to the quantity and spatial organization of PC and PE species in retina were determined …

Cyclic Peptide-Gadolinium Nanoparticles For Enhanced Intracellular Delivery, Amir Nasrolahi Shirazi, Shang Eun Park, Shirin Rad, Luiza Baloyan, Dindyal Mandal, Muhammad Imran Sajid, Ryley Hall, Sandeep Lohan, Khalid Zoghebi, Keykavous Parang, Rakesh Tiwari

Pharmacy Faculty Articles and Research

A cyclic peptide containing one cysteine and five alternating tryptophan and arginine amino acids [(WR)₅C] was synthesized using Fmoc/tBu solid-phase methodology. The ability of the synthesized cyclic peptide to produce gadolinium nanoparticles through an in situ one-pot mixing of an aqueous solution of GdCl₃ with [(WR)₅C] peptide solution was evaluated. Transmission electron microscopy showed the formed peptide-Gd nanoparticles in star-shape morphology with a size of ~250 nm. Flow cytometry investigation showed that the cellular uptake of a cell-impermeable fluorescence-labeled phosphopeptide (F′-GpYEEI, where F′ = fluorescein) was approximately six times higher in the presence of [(WR) …

Cancer-Targeting Immunostimulatory Peptides As An Immunotherapeutic Approach To Cancer, Rachel Montel

Seton Hall University Dissertations and Theses (ETDs)

This dissertation reports the synthesis and biological applications of bifunctional trimeric peptides with B7H6-derived NKp30 binding motifs that serve to activate an immunocytotoxic response in natural killer cells and a GRP78-binding motif that can target tumors that express surface GRP78. In this manner the cancer-targeting immunostimulatory peptides are anticipated to directly bind and activate effector NK92-MI cells while also recognizing and binding to target A549 tumor cells to facilitate NK cell-dependent immunocytotoxicity of the targeted tumors. The NKp30 binding peptide motifs are derived from the tumor associated B7H6 antigen that is often downregulated or shed from the surface of tumors …

Directed Evolution Of Macrocyclic Peptides For Inhibition Of Autophagy, Joshua Gray

Dissertations and Theses (Open Access)

In recent decades it has become increasingly clear that induction of autophagy plays an important role in the development of treatment resistance and dormancy in many cancer types. Chloroquine (CQ) and hydroxychloroquine (HCQ), two autophagy inhibitors in clinical trials, suffer from poor pharmacokinetics and high toxicity at therapeutic dosages. This has prompted intense interest in the development of targeted autophagy inhibitors to re-sensitize disease to treatment with minimal impact on normal tissue. We utilized Scanning Unnatural Protease Resistant (SUPR) mRNA display to develop macrocyclic peptides targeting the autophagy protein LC3. The resulting peptides bound LC3A and LC3B—two essential components of …

Comparative Molecular Transporter Properties Of Cyclic Peptides Containing Tryptophan And Arginine Residues Formed Through Disulfide Cyclization, Eman H. M. Mohammed, Dindyal Mandal, Saghar Mozaffari, Magdy Abdel-Hamied Zahran, Amany Mostafa Osman, Rakesh Kumar Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

We have previously reported cyclic cell-penetrating peptides [WR]₅ and [WR]₄ as molecular transporters. To optimize further the utility of our developed peptides for targeted therapy in cancer cells using the redox condition, we designed a new generation of peptides and evaluated their cytotoxicity as well as uptake behavior against different cancer cell lines. Thus, cyclic [C(WR)_xC] and linear counterparts (C(WR)_xC), where x = 4–5, were synthesized using Fmoc/tBu solid-phase peptide synthesis, purified, and characterized. The compounds did not show any significant cytotoxicity (at 25 µM) against ovarian (SK-OV-3), leukemia (CCRF-CEM), gastric adenocarcinoma (CRL-1739), breast …

A Native Function For Ran Translation And Cgg Repeats In Regulating Fragile X Protein Synthesis, Caitlin M. Rodriguez, Shannon E. Wright, Michael G. Kearse, Jill M. Haenfler, Brittany N. Flores, Yu Liu, Marius F. Ifrim, M. Rebecca Glineburg, Amy Krans, Paymaan Jafar-Nejad, Michael A. Sutton, Gary J. Bassell, Jack M. Parent, Frank Rigo, Sami J. Barmada, Peter K. Todd

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Repeat-associated non-AUG-initiated translation of expanded CGG repeats (CGG RAN) from the FMR1 5′-leader produces toxic proteins that contribute to neurodegeneration in fragile X-associated tremor/ataxia syndrome. Here we describe how unexpanded CGG repeats and their translation play conserved roles in regulating fragile X protein (FMRP) synthesis. In neurons, CGG RAN acts as an inhibitory upstream open reading frame to suppress basal FMRP production. Activation of mGluR5 receptors enhances FMRP synthesis. This enhancement requires both the CGG repeat and CGG RAN initiation sites. Using non-cleaving antisense oligonucleotides (ASOs), we selectively blocked CGG RAN. This ASO blockade enhanced endogenous FMRP expression in human …

Elucidating Molecular Function Of Mithramycin And Analogues For The Treatment Of Ews-Ets Expressing Cancers, Reiya Hayden

Theses and Dissertations--Pharmacy

Introduction: Chromosomal translocations are common in cancer. In many cancers such as prostate cancer, leukemia and Ewing sarcoma, chromosomal translocations are the main driver of malignancy. Ewing sarcoma is a cancer diagnosed mostly in children and adolescents that has very grim outcomes for patients with metastasis and recurrent disease. Malignancy in Ewing sarcoma is due to EWS-FLI1, an aberrant transcription factor that is the result of a chromosomal translocation. EWS-FLI1 is the main driver of oncogenesis in Ewing sarcoma and has been the target of many drugs developed to treat the disease. Mithramycin (MTM) was identified as a potent inhibitor …

Alzheimer's And Amyloid Beta: Amyloidogenicity And Tauopathy Via Dyshomeostatic Interactions Of Amyloid Beta, Jordan Tillinghast

Senior Honors Theses

This paper reviews functions of Amyloid-β (Aβ) in healthy individuals compared to the consequences of aberrant Aβ in Alzheimer’s disease (AD). As extraneuronal Aβ accumulation and plaque formation are characteristics of AD, it is reasonable to infer a pivotal role for Aβ in AD pathogenesis. Establishing progress of the disease as well as the mechanism of neurodegeneration from AD have proven difficult (Selkoe, 1994). This thesis provides evidence suggesting the pathogenesis of AD is due to dysfunctional neuronal processes involving Aβ’s synaptic malfunction, abnormal interaction with tau, and disruption of neuronal homeostasis. Significant evidence demonstrates that AD symptoms are partially …

A Systematic Comparison Of Lipopolymers For Sirna Delivery To Multiple Breast Cancer Cell Lines: In Vitro Studies, Hamidreza Montazeri Aliabadi, Remant Bahadur Kc, Emira Bousoik, Ashley Barbarino, Bindu Thapa, Melissa Coyle, Parvin Mahdipoor, Hasan Uludağ

Pharmacy Faculty Articles and Research

Small interfering RNA (siRNA) therapy is a promising approach for treatment of a wide range of cancers, including breast cancers that display variable phenotypic features. To explore the general utility of siRNA therapy to control aberrant expression of genes in breast cancer, we conducted a detailed analysis of siRNA delivery and silencing response in vitro in 6 separate breast cancer cell models (MDA-MB-231, MDA-MB-231-KRas-CRM, MCF-7, AU565, MDA-MB-435 and MDA-MB-468 cells). Using lipopolymers for siRNA complexation and delivery, we found a large variation in siRNA delivery efficiency depending on the specific lipopolymer used for siRNA complexation and delivery. Some lipopolymers were …

Dormant Pathogenic Cd4(+) T Cells Are Prevalent In The Peripheral Repertoire Of Healthy Mice, Anna Cebula, Michal Kuczma, Edyta Szurek, Maciej Pietrzak, Natasha Savage, Wessam R. Elhefnawy, Grzegorz Rempala, Piotr Kraj, Leszek Ignatowicz

Computer Science Faculty Publications

Thymic central tolerance eliminates most immature T cells with autoreactive T cell receptors (TCR) that recognize self MHC/peptide complexes. Regardless, an unknown number of autoreactive CD4+Foxp3⁻ T cells escape negative selection and in the periphery require continuous suppression by CD4+Foxp3⁺ regulatory cells (Tregs). Here, we compare immune repertoires of Treg-deficient and Treg-sufficient mice to find Tregs continuously constraining one-third of mature CD4⁺Foxp3⁻ cells from converting to pathogenic effectors in healthy mice. These dormant pathogenic clones frequently express TCRs activatable by ubiquitous autoantigens presented by class II MHCs on conventional dendritic cells, including selfpeptides that select …

Short Amylin Receptor Antagonist Peptides Improve Memory Deficits In Alzheimer’S Disease Mouse Model, Rania Soudy, Ryoichi Kimura, Aarti Patel, Wen Fu, Kamaljit Kaur, David Westaway, Jing Yang, Jack Jhamandas

Pharmacy Faculty Articles and Research

Recent evidence supports involvement of amylin and the amylin receptor in the pathogenesis of Alzheimer’s disease (AD). We have previously shown that amylin receptor antagonist, AC253, improves spatial memory in AD mouse models. Herein, we generated and screened a peptide library and identified two short sequence amylin peptides (12–14 aa) that are proteolytically stable, brain penetrant when administered intraperitoneally, neuroprotective against Aβ toxicity and restore diminished levels of hippocampal long term potentiation in AD mice. Systemic administration of the peptides for five weeks in aged 5XFAD mice improved spatial memory, reduced amyloid plaque burden, and neuroinflammation. The common residue SQELHRLQTY …

Edb-Fn Targeted Peptide–Drug Conjugates For Use Against Prostate Cancer, Shang Eun Park, Kiumars Shamloo, Timothy A. Kristedja, Shaban Darwish, Marco Bisoffi, Keykavous Parang, Rakesh Tiwari

Pharmacy Faculty Articles and Research

Prostate cancer (PCa) is the most common malignancy in men and is the leading cause of cancer-related male mortality. A disulfide cyclic peptide ligand [CTVRTSADC] 1 has been previously found to target extra domain B of fibronectin (EDB-FN) in the extracellular matrix that can dierentiate aggressive PCa from benign prostatic hyperplasia. We synthesized and optimized the stability of ligand 1 by amide cyclization to obtain [KTVRTSADE] 8 using Fmoc/tBu solid-phase chemistry. Optimized targeting ligand 8 was found to be stable in phosphate buered saline (PBS, pH 6.5, 7.0, and 7.5) and under redox conditions, with a half-life longer than 8 …

Molecular Recognition Of M1-Linked Ubiquitin Chains By Native And Phosphorylated Uban Domains, Lina Herhaus, Henry Van Den Bedem, Sean Teng, Innokentiy Maslennikov, Soichi Wakatsuki, Ivan Dikic, Simin Rahighi

Pharmacy Faculty Articles and Research

Although the Ub-binding domain in ABIN proteins and NEMO (UBAN) is highly conserved, UBAN-containing proteins exhibit different Ub-binding properties, resulting in their diverse biological roles. Post-translational modifications further control UBAN domain specificity for poly-Ub chains. However, precisely, how the UBAN domain structurally confers such functional diversity remains poorly understood. Here we report crystal structures of ABIN-1 alone and in complex with one or two M1-linked di-Ub chains. ABIN-1 UBAN forms a homo-dimer that provides two symmetrical Ub-binding sites on either side of the coiled-coil structure. Moreover, crystal structures of ABIN1 UBAN in complex with di-Ub chains reveal a concentration-dependency of …

Assessment Of Physical Fitness After Bariatric Surgery And Its Association With Protein Intake And Type Of Cholecalciferol Supplementation, Hendrika J M Smelt, Sjaak Pouwels, Alper Celik, Adarsh Gupta, Johannes F Smulders

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Background: Several studies showed that there is a relationship between vitamin and mineral status and muscle strength. In particular this is the case for handgrip strength (HS) and vitamin D deficiency. In bariatric surgery there is a risk of decrease in muscle strength after surgery and also vitamin and mineral deficiencies are not uncommon. The aim of this study is to assess the effect of low vitamin 25 (OH) cholecalciferol levels, high dose cholecalciferol supplementation regime and protein intake on physical fitness, measured using handgrip strength (HS) and the shuttle walk run test (SWRT). Methods: For this retrospective …

Caspases And Cancer: Connections Through Circular Dichroism Spectroscopy, Sarah M. Hethcox

Honors College Theses

While excessive cell death inevitably leads to negative effects, the endurance of damaged cells in the presence of death signals can be equally detrimental to health. Apoptosis, or programmed cell death, is a highly regulated process in which cues from within or from outside a cell can trigger an irreversible sequence of signals that carry out cell destruction known as the apoptotic cascade. A group of enzymes called caspases play a vital role in this cascade with some participating as initiators and others acting as effectors of protein cleavage and intracellular breakdown. Although it is normal for the activity of …

Effect Of Tyrosine On The Productivity Of Pc12 Cells By Measuring Extracellular Atp Release, Sabrina Burkholder, Mary Rapmund, David Fogel, Jon Flees

Student Scholar Symposium Abstracts and Posters

Given the challenge to “reverse-engineer the brain”, our group tried to address the problems of a lack of long term focus and attention span. Tyrosine was determined to aid in mental focus and brain productivity as it is a precursor to the neurotransmitter Dopamine. Given that Tyrosine is naturally occurring in the body, it is preferable to add to the body, whereas a substance like Adderall has negative effects, including increased heart rate that, over time, can cause cardiovascular damage. Drawing connections between in increase ATP and an increased ability to focus and perform under stress, extracellular ATP secretion of …

Synthesis And Antiproliferative Activities Of Conjugates Of Paclitaxel And Camptothecin With A Cyclic Cell-Penetrating Peptide, Naglaa Salem El-Sayed, Amir Nasrolahi Shirazi, Muhammad Imran Sajid, Shang Eun Park, Keykavous Parang, Rakesh Tiwari

Pharmacy Faculty Articles and Research

Cell-penetrating peptide [WR]5 has been previously shown to be an efficient molecular transporter for various hydrophilic and hydrophobic molecules. The peptide was synthesized using Fmoc/tBu solid-phase chemistry, and one arginine was replaced with one lysine to enable the conjugation with the anticancer drugs. Paclitaxel (PTX) was functionalized with an esterification reaction at the C20 hydroxyl group of PTX with glutaric anhydride and conjugated with the cyclic peptide [W(WR)4K(bAla)] in DMF to obtain the peptide-drug conjugate PTX1. Furthermore, camptothecin (CPT) was modified at the C(20)-hydroxyl group through the reaction with triphosgene. Then, it was conjugated with two functionalized cyclic peptides through …

The Pharmabiotic For Phenylketonuria: Development Of A Novel Therapeutic, Chloé Elizabeth Lebegue

Senior Theses

Phenylketonuria, now known as phenylalanine hydroxylase (PAH) deficiency, is a genetic disorder of metabolism affecting approximately one in every 15,000 infants born in the United States. Patients have nonfunctional PAH enzyme secondary to one or more genetic mutations. The enzyme deficit results in destructive supraphysiologic blood phenylalanine levels upon consumption of the essential dietary amino acid phenylalanine. Current standards of care mitigate signs and symptoms of the disorder, but do not approach a cure. The methods for creating a prototype pharmabiotic as an innovative treatment strategy for PAH deficiency are described herein.

DNA molecular cloning techniques were utilized to engineer …